Comprehensive Meta-Analysis of DES vs Comprehensive Meta-Analysis of DES vs. BMS Randomized Trials and Registries Ajay J. Kirtane, M.D., S.M. Gregg W. Stone, M.D.

Conflict of Interest Disclosure Ajay J. Kirtane Past honorarium from Boston Scientific Corporation (modest) Consultant/Speaker: Medtronic Vascular, Abbott Vascular (modest) Gregg W. Stone Research grants from Boston Scientific and Abbott Vascular

Background: DES vs. BMS RCTs In most individual RCTs, DES have reduced the rates of TLR and TVR compared to BMS, with no significant differences in death or MI However, individual RCTs are underpowered to assess low frequency endpoints RCTs, particularly the pivotal RCTs leading to regulatory approval, have been criticized for not reflecting “real-world” DES use RCT outcomes may vary based upon differences in enrollment criteria (e.g. “on-label” vs. “off- label”), the amount of routine angiographic FU, and with the duration of clinical FU

Background: DES vs. BMS Registries In order to address issues of both sample size as well as generalizability to the “real-world”, numerous observational and registry comparisons of DES vs. BMS have been undertaken The outcomes from these studies have varied While more generalizable than RCTs, the DES vs. BMS registries are heterogeneous, with differences in design and analysis methodology (e.g. adjusted vs. unadjusted, type of adjustment) Registry outcomes may also vary based upon the types of patients enrolled (e.g. all comers vs. just ACS or high risk), and the duration of clinical FU

Persistent Questions: DES vs. BMS While some of the alarm generated after ESC 2006 has been mitigated by analyses of patient-level data from the “on-label” RCTs*, there remains concern regarding DES outcomes in “off-label” patients and lesions, and with uncontrolled use Are DES safe in higher risk off-label pts and in the unregulated environment of real-world use? Are the benefits of DES in reducing TVR as robust in the real-world as in the RCTs, given the impact of routine angio FU and the oculostenotic reflex in many RCTs? *Stone et al, Kastrati et al, Spaulding et al, Mauri et al N Engl J Med 2007; 356(10).

Methods: Goals and Objectives (1) We therefore sought to perform a systematic review and meta-analysis of DES vs. BMS studies To derive summary estimates of all-cause mortality, MI, and TVR in studies with ≥1 year of follow-up To specifically assess differences between RCT and registry safety and effiacy with regard to these endpoints

Methods: Goals and Objectives (2) Randomized Trials To assess differences between RCTs according to “on-label” vs. “off-label” use, duration of FU, and baseline risk Registries / Observational Analyses To assess differences in the estimates derived from registries using unadjusted and adjusted analyses (and according to the types of adjustment) To assess differences between registries according to duration of FU, and baseline risk To assess differences in effect size estimates between the RCTs and registries for each endpoint

Methods: Inclusion Criteria English language RCTs or registries which reported a direct comparison of DES (commercialized formulations of SES and PES only) vs. BMS. Criteria for each study: ≥100 patients total Mortality reported (± MI and/or TVR) ≥1 year of cumulative follow-up reported, with the outcome assessed at the same time point in both comparator arms

Methods: Exclusion Criteria “DES era” vs. pure “BMS era” studies in which the DES era group did not exclude BMS pts Excepting intent-to-treat RCTs Study used a control group from another study already in the meta-analysis Study was itself a meta-analysis (although data abstracted from individual studies in a published meta-analysis could be used)

Methods: Search Strategy (1) 2 PUBMED searches Focused: (eluting stent OR DES OR drug-eluting stent) AND (bare OR uncoated OR standard OR BMS) AND (("2002"[PDat] : "2008"[PDat]) AND (Humans[Mesh]) AND (English[lang])) AND (coronary) NOT (cost-effectiveness) NOT review[pt] NOT case reports[pt] NOT editorial[pt] NOT comment[pt] Broad: stent AND bare AND (eluting OR sirolimus OR paclitaxel) Cochrane database Eurointervention journal

Methods: Search Strategy (2) Abstracts/presentations from 2007 meetings: ACC SCAI/I2 Summit ESC TCT AHA Data requested from study PI’s for large registries For most updated data Where not publicly available or to clarify methodology

Methods: Analysis Pre-specified separate analysis of RCTs and Registries performed given clinical heterogeneity RCTs: Direct randomization to DES vs. BMS Registries: Non-rand comparison of DES vs. BMS (including non-rand comparisons within a RCT) All analyses cumulative No landmarks Single time point estimate for each study assuming constant hazard of DES vs. BMS through study period (hence use of HR or RR as the estimate) Higher quality estimate picked for primary analyses (adjusted > unadjusted)

Methods: Statistical Analysis All analyses were performed at The Cardiovascular Research Foundation/Columbia University Models (both reported): Fixed effects (Inverse-Variance weighted) Random effects (DerSimonian and Laird)* Fixed effects model was considered the primary model if significant heterogeneity was not present; otherwise random effects was considered primary Formal heterogeneity testing was performed using the I2 statistic; heterogeneity was defined as I2 ≥ 25% *Weights displayed in figures are based upon the primary model used

Selected Excluded Studies GRACE Non-landmark data not available (PI contacted as well) Unequal follow-up in comparator arms (data not presented at fixed timepoint) RRISC Less than 100 patients Medicare Data Comparison of pre-DES era with post-DES rather than DES vs. BMS This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 14

All-Cause Mortality: All RCTs 8,867 patients, 21 trials Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Random Effects *Fixed Effects (I2=0.0%) 0.97 (0.81,1.15) 0.97 (0.81,1.15), p=0.72 Favors DES Favors BMS Mean f/u 2.9 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 15

All-Cause Mortality: RCTs (On-Label) 4,818 patients, 10 trials Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Random Effects *Fixed Effects (I2=0.0%) 1.05 (0.84,1.30) 1.05 (0.84,1.30), p=0.69 Favors DES Favors BMS Mean f/u 4.0 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 16

All-Cause Mortality: RCT’s (Off-Label) 4,049 patients, 12 trials Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Random Effects *Fixed Effects (I2=0.0%) 0.84 (0.62,1.13) 0.84 (0.62,1.13), p=0.24 Favors DES Favors BMS Mean f/u 1.5 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 17

All-Cause Mortality: All Registries 161,232 patients, 28 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=70.1%) Fixed Effects 0.80 (0.72,0.88), p<0.001 0.83 (0.79,0.86) Favors DES Favors BMS Mean f/u 2.5 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 18

All-Cause Mortality: Unadjusted Registries 122,989 patients, 22 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=75.3%) Fixed Effects 0.70 (0.63,0.78), p<0.001 0.69 (0.66,0.72) Favors DES Favors BMS Mean f/u 2.1 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 19

All-Cause Mortality: Adjusted Registries 134,534 patients, 18 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=76.6%) Fixed Effects 0.80 (0.72,0.90), p<0.001 0.82 (0.79,0.86) Favors DES Favors BMS Mean f/u 2.7 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 20

All-Cause Mortality: Registries Begg’s Funnel Plot p=0.92 log(Hazard Ratio) Standard Error of log(Hazard Ratio) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Ajay J. Kirtane and Gregg W. Stone, 2008 21

Ajay J. Kirtane and Gregg W. Stone, 2008 MI: All RCTs 8,850 patients, 20 trials Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Random Effects *Fixed Effects (I2=3.0%) 0.94 (0.78,1.13) 0.94 (0.79,1.13), p=0.54 Favors DES Favors BMS Mean f/u 2.9 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 22

Ajay J. Kirtane and Gregg W. Stone, 2008 MI: RCTs (On Label) 4,318 patients, 9 trials Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Random Effects *Fixed Effects (I2=0.0%) 1.03 (0.81,1.30) 1.03 (0.81,1.30), p=0.82 Favors DES Favors BMS Mean f/u 4.4 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 23

Ajay J. Kirtane and Gregg W. Stone, 2008 MI: RCT’s (Off Label) 4,532 patients, 12 trials Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Random Effects *Fixed Effects (I2=25.5%) 0.77 (0.54,1.10) 0.83 (0.62,1.10), p=0.19 Favors DES Favors BMS Mean f/u 1.5 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 24

Ajay J. Kirtane and Gregg W. Stone, 2008 MI: All Registries 129,955 patients, 24 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=57.9%) Fixed Effects 0.89 (0.80,0.98), p=0.023 0.96 (0.91,1.01) *MI is QWMI in Washington Hospital Center, RESTEM Favors DES Favors BMS Mean f/u 2.5 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 25

MI: Unadjusted Registries 88,221 patients, 18 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=77.8%) Fixed Effects 0.83 (0.70,0.97), p=0.023 0.88 (0.83,0.93) *MI is QWMI in Washington Hospital Center, RESTEM Favors DES Favors BMS Mean f/u 2.0 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 26

MI: Adjusted Registries 107,294 patients, 14 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=60.8%) Fixed Effects 0.91 (0.81,1.01), p=0.083 0.96 (0.91,1.01) *MI is QWMI in Washington Hospital Center Favors DES Favors BMS Mean f/u 2.8 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 27

Ajay J. Kirtane and Gregg W. Stone, 2008 TVR: All RCTs 7,291 patients, 16 trials Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=53.2%) Fixed Effects 0.45 (0.37,0.54), p<0.001 0.51 (0.45,0.57) Favors DES Favors BMS Mean f/u 3.2 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 28

TVR: RCTs Meta-Regression on Percent Angiographic F/U p=0.73 *Hazard Ratio p=0.73 Percentage of Patients with Angiographic F/U *log(HR) regressed on percentage of pts with angiographic f/u; figure displayed on exponentiated scale Ajay J. Kirtane and Gregg W. Stone, 2008

Ajay J. Kirtane and Gregg W. Stone, 2008 TVR: All Registries 73,819 patients, 17 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=71.2%) Fixed Effects 0.53 (0.47,0.61), p<0.001 0.57 (0.54,0.60) Favors DES Favors BMS Mean f/u 2.2 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 30

TVR: Unadjusted Registries 55,531 patients, 12 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=88.9%) Fixed Effects 0.60 (0.48,0.74), p<0.001 0.73 (0.69,0.77) Favors DES Favors BMS Mean f/u 2.2 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 31

TVR: Adjusted Registries 63,456 patients, 11 registries Estimate (95% CI) Weight (%) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) *Random Effects (I2=79.4%) Fixed Effects 0.54 (0.46,0.63), p<0.001 0.58 (0.54,0.61) Favors DES Favors BMS Mean f/u 2.2 yrs Ajay J. Kirtane and Gregg W. Stone, 2008 32

Summary: DES vs. BMS Treatment Effect Estimates Mortality MI TVR RCTs 8,867 pts, 21 trials 8,850 pts, 20 trials 7,291 pts, 16 trials Fixed effects Random effects 0.97 0.94 0.51 0.45* Registries 161,232 pts, 28 studies 129,955 pts, 24 studies 73,819 pts, 17 studies 0.83 0.80* 0.96 0.89* 0.57 0.53* <1.0  DES better

Study Limitations Randomized trial analyses are still underpowered to assess these clinical endpoints Registry analyses are based upon observational, non-randomized analyses Potential for residual confounding Significant heterogeneity, despite attempts to address this through random effects models, meta-regression and sensitivity analyses Analysis was primarily of summary-level data and included unpublished studies Use of hazard ratio / relative risk assumes constant hazards throughout the FU period

Conclusions (1) In 22 RCTs in which 9,470 pts were randomized to DES or BMS and followed for ≥1 yr, DES resulted in: Non significant 3% and 6% reductions in mortality and MI respectively A highly significant 55% reduction in TVR In 30 registries in which 174,302 pts were treated with either DES or BMS (non-randomized) and followed for ≥1 yr, DES was associated with: A highly significant 20% reduction in mortality A significant 11% reduction in MI A highly significant 47% reduction in TVR

Conclusions (2) The favorable results of DES from the RCT and registry analysis populations were robust and consistent for both on-label and off-label use, and for clinical f/u extending to 3-4 years These findings, derived from more than 180,000 pts treated in 52 studies, strongly suggest that DES are safe for both on-label and off-label use, and have comparable efficacy in both RCTs and in the “real-world”